Targeting Protein Kinase C (PKC) in Physiology and Cancer of the Gastric Cell System

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Abstract:

Protein kinase C (PKC) family members are multifunctional kinases that have been implicated in many cell biological and physiological tasks including acid, pepsinogen, and mucous production. Through the use of small-molecule PKC modulators, PKC has been found to be involved in gene expression, the control of cytoskeleton, membrane and secretagogue-dependent signal transduction for secretion of acid. Gastric carcinoma and adenocarcinoma cells often show dysregulated PKC-dependent cell signal transduction compared to normal gastric cells. Moreover, PKC was the first known target of tumor promoting phorbol esters. These findings support PKC as a potential chemotherapy target in gastric cancer. Various approaches have been launched in directly targeting PKC for chemotherapy of gastric cancer. The macrocyclic lactone bryostatin-1 is a promising agent that acts as a modulator of PKC activity, and enhances the effect of chemotherapeutic agents such as paclitaxel. This article provides an overview of the findings to date regarding the physiological role of PKC in the gastric cell system by various pharmacological approaches and examines PKC as a target in gastric (adeno-)carcinoma chemotherapy.

Keywords: bis(indolyl)maleimide; bryostatin; chemotherapy; gastric acid secretion; gastric cancer; indolocarbazole; phorbol ester; protein kinase C

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708784310413

Affiliations: Medizinische Hochschule Hannover,Zentrum Pharmakologie und Toxikologie, Institut fur Pharmakologie OE 5320, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.

Publication date: May 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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